RATIONALE: Genetically influenced alcohol sensitivity is thought to be an important risk factor for the development of alcoholism. An effective first step for identifying genes that mediate variation in alcohol sensitivity is through quantitative trait loci (QTL) mapping in model organisms. OBJECTIVE: Fourteen provisional QTLs related to alcohol sensitivity were previously mapped in an F2 derived from the IHAS1 and ILAS1 rat lines. The objective of the current study was to confirm those QTLs in an independently derived F2 and in congenics that were bred for two of the loci. MATERIALS AND METHODS: IHAS1 X ILAS1 F2 (n=450) were tested for alcohol-induced loss of righting reflex (LORR), blood ethanol concentration at regain of righting reflex (BECRR), sensitivity and acute tolerance on the Rotarod, and neurotensin receptor density (NTR1). Rats were genotyped at the 14 candidate loci and QTL mapping was conducted. Reciprocal congenic strains were bred for loci on chromosomes 2 and 5 and tested for LORR and BECRR. RESULTS: Four LORR QTLs were mapped at the suggestive or significant level (chromosomes 2, 5, 12, and 13). BECRR was mapped to chromosomes 5, 12, and 13 either in the original or current experiment. Results of the congenic experiment also support QTLs for LORR and BECRR on chromosomes 2 and 5. QTLs for NTR1 density and behavior on the Rotarod were not confirmed. CONCLUSIONS: QTL mapping in crosses derived from the IHAS1 and ILAS1 has successfully identified loci related to alcohol sensitivity. Recombinant congenics are now being bred to more finely map the confirmed QTLs.
RATIONALE: Genetically influenced alcohol sensitivity is thought to be an important risk factor for the development of alcoholism. An effective first step for identifying genes that mediate variation in alcohol sensitivity is through quantitative trait loci (QTL) mapping in model organisms. OBJECTIVE: Fourteen provisional QTLs related to alcohol sensitivity were previously mapped in an F2 derived from the IHAS1 and ILAS1 rat lines. The objective of the current study was to confirm those QTLs in an independently derived F2 and in congenics that were bred for two of the loci. MATERIALS AND METHODS: IHAS1 X ILAS1 F2 (n=450) were tested for alcohol-induced loss of righting reflex (LORR), blood ethanol concentration at regain of righting reflex (BECRR), sensitivity and acute tolerance on the Rotarod, and neurotensin receptor density (NTR1). Rats were genotyped at the 14 candidate loci and QTL mapping was conducted. Reciprocal congenic strains were bred for loci on chromosomes 2 and 5 and tested for LORR and BECRR. RESULTS: Four LORR QTLs were mapped at the suggestive or significant level (chromosomes 2, 5, 12, and 13). BECRR was mapped to chromosomes 5, 12, and 13 either in the original or current experiment. Results of the congenic experiment also support QTLs for LORR and BECRR on chromosomes 2 and 5. QTLs for NTR1 density and behavior on the Rotarod were not confirmed. CONCLUSIONS: QTL mapping in crosses derived from the IHAS1 and ILAS1 has successfully identified loci related to alcohol sensitivity. Recombinant congenics are now being bred to more finely map the confirmed QTLs.
Authors: Beth Bennett; Mary Beeson; Lena Gordon; Phyllis Carosone-Link; Thomas E Johnson Journal: Alcohol Clin Exp Res Date: 2002-11 Impact factor: 3.455
Authors: Oduola Abiola; Joe M Angel; Philip Avner; Alexander A Bachmanov; John K Belknap; Beth Bennett; Elizabeth P Blankenhorn; David A Blizard; Valerie Bolivar; Gundrun A Brockmann; Kari J Buck; Jean-Francoise Bureau; William L Casley; Elissa J Chesler; James M Cheverud; Gary A Churchill; Melloni Cook; John C Crabbe; Wim E Crusio; Ariel Darvasi; Gerald de Haan; Peter Dermant; R W Doerge; Rosemary W Elliot; Charles R Farber; Lorraine Flaherty; Jonathan Flint; Howard Gershenfeld; John P Gibson; Jing Gu; Weikuan Gu; Heinz Himmelbauer; Robert Hitzemann; Hui-Chen Hsu; Kent Hunter; Fuad F Iraqi; Ritsert C Jansen; Thomas E Johnson; Byron C Jones; Gerd Kempermann; Frank Lammert; Lu Lu; Kenneth F Manly; Douglas B Matthews; Juan F Medrano; Margarete Mehrabian; Guy Mittlemann; Beverly A Mock; Jeffrey S Mogil; Xavier Montagutelli; Grant Morahan; John D Mountz; Hiroki Nagase; Richard S Nowakowski; Bruce F O'Hara; Alexander V Osadchuk; Beverly Paigen; Abraham A Palmer; Jeremy L Peirce; Daniel Pomp; Michael Rosemann; Glenn D Rosen; Leonard C Schalkwyk; Ze'ev Seltzer; Stephen Settle; Kazuhiro Shimomura; Siming Shou; James M Sikela; Linda D Siracusa; Jimmy L Spearow; Cory Teuscher; David W Threadgill; Linda A Toth; Ayo A Toye; Csaba Vadasz; Gary Van Zant; Edward Wakeland; Robert W Williams; Huang-Ge Zhang; Fei Zou Journal: Nat Rev Genet Date: 2003-11 Impact factor: 53.242
Authors: Bruce H Mandt; Colin Larson; Tina Fay; Pequita Bludeau; Richard M Allen; Richard A Deitrich; Richard A Radcliffe Journal: Alcohol Date: 2017-08-12 Impact factor: 2.405
Authors: Tianna R Hicklin; Peter H Wu; Richard A Radcliffe; Ronald K Freund; Susan M Goebel-Goody; Paulo R Correa; William R Proctor; Paul J Lombroso; Michael D Browning Journal: Proc Natl Acad Sci U S A Date: 2011-04-04 Impact factor: 11.205
Authors: Matthew Packard; Yasser Saad; William T Gunning; Shalini Gupta; Joseph Shapiro; Michael R Garrett Journal: Am J Physiol Renal Physiol Date: 2009-01-28
Authors: Natalie S McGuier; Jennifer A Rinker; Reginald Cannady; Diana B Fulmer; Sara R Jones; Michaela Hoffman; Patrick J Mulholland Journal: Neuropharmacology Date: 2018-05-25 Impact factor: 5.250